Microsimulation models can be used to estimate the effect of screening and changes in population risk on colorectal cancer (CRC) outcomes, offering insights beyond those gained from either observational or randomized studies. Over the past two years, we have built a new microsimulation model for the natural history of CRC, and we are in the process of refining our screening model. We propose to use our model to estimate the impact of CRC screening on observed population trends in CRC incidence and mortality, expanding our focus to include the impact of risk factors on both observed and projected CRC outcomes. Our proposed work centers around three specific aims: Specific Aim 1: Estimating the effect of screening and polypectomy on trends in CRC incidence and mortality within the US population using our population-based microsimulation model. In particular, we will examine the impact of screening as practiced on CRC outcomes, and the potential impact of different guideline recommended screening strategies on CRC outcomes. Specific Aim 2: Extending our natural history model to incorporate the effects of individual risk factors (e.g., smoking, obesity) on CRC outcomes, and extending our screening model to explore the potential impact of new technologies on future trends in CRC outcomes. Explicit incorporation of risk factors is needed to estimate the effect of future changes in risk factors on outcomes, and to assess our Nation's ability to reduce CRC incidence and mortality. We will begin by estimating the effect of changes in a hypothetical risk factor on CRC outcomes, providing critical information about the relationship between risk factors and cancer outcomes. Ultimately, we will estimate the impact of changes in risk on CRC outcomes by building secular trends in risk factor behavior into our models. Specific Aim 3: Collaborating with both CISNET members and other investigators to address policy-relevant questions. Our proposed work is best carried out in collaboration with colleagues in the Cancer Incidence and Surveillance Modeling Network (CISNET). The positive synergy of this group has enabled our team to rapidly develop and implement our microsimulation model for CRC.